Endoscopic ultrasonography-guided gastroenterostomy versus surgical gastrojejunostomy for palliation of malignant gastric outlet obstruction (ENDURO): study protocol for a randomized controlled trial

Background Malignant gastric outlet obstruction (GOO) is a debilitating condition that frequently occurs in patients with malignancies of the distal stomach and (peri)ampullary region. The standard palliative treatment for patients with a reasonable life expectancy and adequate performance status is a laparoscopic surgical gastrojejunostomy (SGJ). Recently, endoscopic ultrasound-guided gastroenterostomy (EUS-GE) emerged as a promising alternative to the surgical approach. The present study aims to compare these treatment modalities in terms of efficacy, safety, and costs. Methods The ENDURO-study is a multicentre, open-label, parallel-group randomized controlled trial. In total, ninety-six patients with gastric outlet obstruction caused by an irresectable or metastasized malignancy will be 1:1 randomized to either SGJ or EUS-GE. The primary endpoint is time to tolerate at least soft solids. The co-primary endpoint is the proportion of patients with persisting or recurring symptoms of gastric outlet obstruction for which a reintervention is required. Secondary endpoints are technical and clinical success, quality of life, gastroenterostomy dysfunction, reinterventions, time to reintervention, adverse events, quality of life, time to start chemotherapy, length of hospital stay, readmissions, weight, survival, and costs. Discussion The ENDURO-study assesses whether EUS-GE, as compared to SGJ, results in a faster resumption of solid oral intake and is non-inferior regarding reinterventions for persistent or recurrent obstructive symptoms in patients with malignant GOO. This trial aims to guide future treatment strategies and to improve quality of life in a palliative setting. Trial registration International Clinical Trials Registry Platform (ICTRP): NL9592. Registered on 07 July 2021. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-023-07522-7.

1 Additional file 3primary and secondary endpoints Primary endpoints 1a.Time to oral intake of soft solids is defined as the number of days until a patient is able to tolerate soft solids without vomiting.Day of intervention is considered day 0. The ability to tolerate oral intake is assessed with the Gastric Outlet Obstruction Scoring System (GOOSS), which is depicted in table 1 [1].Reinterventions may be categorized as follows: -Endoscopic procedures aimed at evaluating and, if applicable, treating anastomotic dysfunction, such as removing impacted food/tissue overgrowth, insertion of a second LAMS after migration of the first, or procedures aimed at creating an alternative route for food passage, such as placement of an enteral stent or creation of a percutaneous jejunostomy or venting gastrostomy, or placement of an oral feeding tube; -Surgical procedures aimed at treating dysfunction of the gastroenteric anastomosis or creating alternative ways for food passage, such as creation of a percutaneous jejunostomy; -Radiologic procedures to treat symptoms of gastric outlet obstruction, such as construction of a percutaneous gastrostomy or jejunostomy; -Initiation of total parenteral nutrition.

Secondary endpoints
2. Technical success is defined as successful creation of a gastroenterostomy by means of the allocated technique (EUS-GE or SGJ).Successful (stent-in-stent) placement of a second Hot AXIOS TM stent during the same procedure after the initial attempt failed is also considered technically successful.If additional techniques, modalities or different type of stents (e.g.selfexpandable metallic stents) were required, it will be regarded as technical failure.
3. Clinical success is defined as relief of symptoms and toleration of soft solids (GOOSS ≥ 2) without vomiting.
4. Gastroenterostomy dysfunction is defined as recurrence of obstructive symptoms (GOOSS 0-1) due to recurrence of GOO at the gastroenterostomy site after initial clinical success, confirmed endoscopically or radiographically.
5. Reintervention is defined as any radiologic, endoscopic or surgical intervention for an adverse event, persistent obstructive symptoms or recurrent obstructive symptoms, that is needed after EUS-GE or SGJ.This includes creating an alternative route to improve or restore adequate nutritional intakeeither through placing a nasal feeding tube, construction of a percutaneous gastrostomy or jejunostomy, or through initiating parenteral nutrition.
6. Time to reintervention for persistence or recurrence of symptoms is defined as the time in days between EUS-GE/SGJ and reintervention for persistence or recurrence of symptoms of GOO (nausea, vomiting, inability to tolerate oral intake).
7. Adverse events (AEs) are specified according to the ASGE lexicon for endoscopic adverse events [2].An adverse event is defined as "an event that prevents completion of the planned procedure and/or results in admission to hospital, prolongation of existing hospital stay, another procedure (needing sedation/anesthesia), or subsequent medical consultation."Severity of AEs is graded according to the Clavien-Dindo Complication Score (severe is defined as ≥ 3B) [3,4].
8. Quality of life will be measured by two cancer specific questionnaires (core-questionnaire EORTC QLQ-C30 supplemented with a disease-specific module EORTC QLQ-STO22 focusing on gastric complaints) to measure health related quality of life of cancer patients [5,6].In addition, the EQ-5D-3L questionnaire is used in cost-effectiveness analysis [7].

Table 1
Gastric Outlet Obstruction Scoring System